Photodynamic therapy composition

Patent metadata

Field	Value
Publication number	US-10709794-B2
Application number	US-201916279326-A
Country	US
Kind code	B2
Filing date	Feb 19, 2019
Priority date	Feb 15, 2013
Publication date	Jul 14, 2020
Grant date	Jul 14, 2020

Abstract

A phthalocyanine compound or targeted conjugate thereof having the formula (I).

First claim

Having described the invention, we claim:

1. A method of treating cancer comprising:
(a) administering to a subject with cancer a therapeutically effective amount of a composition comprising a pharmaceutical composition comprising a phthalocyanine compound or targeted conjugate thereof having the formula (I):

wherein X 1 is hydrogen or includes a targeting moiety directly or indirectly coupled or conjugated to the thiol group;
R 1 , R 4 , R 5 , R 8 , R 9 , R 12 , R 13 , and R 16 are each independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, and methyl;
R 2 , R 3 , R 6 , R 7 , R 10 , R 11 , R 14 , and R 15 are each independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, carboxy, aryl, heteroaryl, carbocyclyl, heterocyclyl, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 alkoxy, C 1-6 acyl, C 1-6 alkylcarbonyloxy, C 1-6 carbocyclylalkyl, C 1-6 aminoalkyl, alkylamino, C 1-6 thioalkyl, C 1-6 alkylthio, C 1-6 hydroxyalkyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylaminocarbonyl, and C 1-6 alkylcarbonylamino; and pharmaceutically acceptable salts thereof; and
(b) exposing the phthalocyanine compound or targeted conjugate thereof to light, thereby inducing the cytotoxic effects of the phthalocyanine compound or targeted conjugate thereof.

2. The method of claim 1 , wherein R 1 -R 16 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, and methyl.

3. The method of claim 1 , the pharmaceutical composition having the formula (II):

wherein X 1 is hydrogen or includes a targeting moiety directly or indirectly coupled or conjugated to the thiol group;
R 1 , R 4 , R 5 , R 8 , R 9 , R 12 , R 13 , and R 16 are each independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, and methyl;
R 2 , R 3 , R 6 , R 7 , R 10 , R 11 , R 14 , and R 15 are each independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, carboxy, aryl, heteroaryl, carbocyclyl, heterocyclyl, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 alkoxy, C 1-6 acyl, C 1-6 alkylcarbonyloxy, C 1-6 carbocyclylalkyl, C 1-6 aminoalkyl, C 1-6 alkylamino, C 1-6 thioalkyl, C 1-6 alkylthio, C 1-6 hydroxyalkyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylaminocarbonyl, and C 1-6 alkylcarbonylamino; and pharmaceutically acceptable salts thereof.

4. The method of claim 3 , wherein R 1 -R 16 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, and methyl.

5. The method of claim 1 , the pharmaceutical composition having the formula (III):

wherein X 1 is hydrogen or includes a targeting moiety directly or indirectly coupled or conjugated to the thiol group;
R 1 , R 4 , R 5 , R 8 , R 9 , R 12 , R 13 , and R 16 are each independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, and methyl;
R 2 , R 3 , R 6 , R 7 , R 10 , R 11 , R 14 , and R 15 are each independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, carboxy, aryl, heteroaryl, carbocyclyl, heterocyclyl, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 alkoxy, C 1-6 acyl, C 1-6 alkylcarbonyloxy, C 1-6 carbocyclylalkyl, C 1-6 aminoalkyl, C 1-6 alkylamino, C 1-6 thioalkyl, C 1-6 alkylthio, C 1-6 hydroxyalkyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylaminocarbonyl, and C 1-6 alkylcarbonylamino; and pharmaceutically acceptable salts thereof.

6. The method of claim 5 , wherein R 1 -R 16 are independently selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, thiol, amino, and methyl.

7. The method of claim 1 , the pharmaceutical composition having the formula (IV):

and pharmaceutically acceptable salts thereof.

8. The method of claim 1 , wherein the phthalocyanine compound is coupled or conjugated to a targeting moiety.

9. The method of claim 8 , wherein the targeting moiety is selected from the group consisting of a polypeptide, polynucleotide, small molecule, elemental compound, antibody, and antibody fragments.

10. The method of claim 8 , wherein the phthalocyanine compound is directly coupled or conjugated to a targeting moiety.

11. The method of claim 8 , wherein the phthalocyanine compound is coupled or conjugated to a targeting moiety via a linker.

12. The method of claim 8 , wherein the targeting moiety is coupled or conjugated to the thiol group of the phthalocyanine compound.

13. The method of claim 8 , the targeting moiety comprising a prostate specific membrane antigen (PSMA) ligand.

14. The method of claim 13 , the PSMA ligand comprising a PSMA-1 ligand.

15. The method of claim 1 , the pharmaceutical composition formulated for systemic administration.

16. The method of claim 15 , wherein the pharmaceutical composition is administered systemically.

17. The method of claim 1 , wherein the cancer is selected from the group consisting of squamous cell carcinoma, non-small cell carcinoma, small cell carcinoma, basal cell carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, adenocarcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, undifferentiated carcinoma, bronchogenic carcinoma, melanoma, renal cell carcinoma, hepatoma-liver cell carcinoma, bile duct carcinoma, cholangiocarcinoma, papillary carcinoma, transitional cell carcinoma, choriocarcinoma, semonoma, embryonal carcinoma, mammary carcinomas, gastrointestinal carcinoma, colonic carcinomas, bladder carcinoma, prostate carcinoma, squamous cell carcinoma of the neck and head region, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordosarcoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, synoviosarcoma and mesotheliosarcoma; myeloma, acute myelogenous leukemia, chronic lymphocytic leukemia, granulocytic leukemia, monocytic leukemia, lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, malignant lymphoma, plasmocytoma, reticulum cell sarcoma, Hodgkin's disease, glioma, glioblastoma multiform, meningoma, medulloblastoma, schwannoma and epidymoma.

18. The method of claim 1 , wherein the cancer is characterized by PSMA expression.

19. The method of claim 17 , wherein the cancer is selected from the group consisting of renal carcinoma, transitional cell carcinoma of the urinary bladder, testicular embryonal carcinoma, colonic adenocarcinoma, neuroendocrine carcinoma, gliobastoma multiforme, malignant melanoma, pancreatic ductal carcinoma, non-small cell lung carcinoma, soft tissue carcinoma, breast carcinoma, and prostatic adenocarcinoma.

20. The method of claim 19 , wherein the cancer is metastatic prostate cancer.

21. A method of treating prostate cancer comprising:
(a) administering to a subject with prostate cancer a therapeutically effective amount of a composit

Assignees

• Univ Case Western Reserve

Inventors

• Basilion James
• Wang Xinning
• Burda Clemens

Classifications

• A61K41/0071 Primary

  PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines · CPC title

• A61K31/695

  Silicon compounds · CPC title

• A61K47/64 Primary

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K49/0036

  Porphyrins (used in photodynamic therapy A61K41/0071 or A61K41/0076; used as targeting group or modifying agent for targeting a therapeutic compound A61K47/546) · CPC title

• A61K47/645

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title